The present invention relates to a process for the carbonylation of an alkyl halide to form an alkyl .alpha.-keto-carboxylic acid as the predominant product.
The practical value of such .alpha.-keto-carboxylic acids is that they can be used to prepare the corresponding .alpha.-amino-acids of .alpha.-hydroxy acids which play an important role in biochemistry.
The preparation of e-keto-carboxylic acids and their derivatives has been the subject of a large number of investigations. According to Rodd, The Chemistry of Carbon Compounds (1952 edition), Vol. 1, pages 227-229, the following methods of preparation are available:
gentle oxidation of .alpha.-hydroxyacids containing a secondary hydroxyl group, or by the enzymatic deamination of .alpha.-amino-acids; PA0 hydrolysis of an acyl cyanide; PA0 hydrolysis of .alpha.-oximino-esters; PA0 from glycidic acid esters on treatment with benzene saturated with boron trifluoride; PA0 from .alpha.,.beta.-dibromocarboxylic acids by forming a piperidine addition compound followed by hydrolysis; PA0 from .alpha.-keto-acetals by ultraviolet irradiation in the presence of N-bromosuccinimide; PA0 from .alpha.-bromomethylketones by boiling with selenium dioxide in absolute methanol or ethanol; PA0 from carboxylic acid esters by oxidation with selenium dioxide; PA0 permanganate oxidation of vinyl ketones; PA0 from carboxylic acid esters by condensation with oxalic ester followed by decarboxylation; PA0 from aldehydes via 5-alkylidene-2-thio-oxazolid-4-ones or by reaction with methyl methoxyacetate; PA0 hydrolysis of azlactones or acetamido-acrylic acids; PA0 hydrolysis of the reaction product of Grignard reagents on diethyl-oxamic ester; PA0 oxidation of .alpha.-hydroxyacid esters containing two .beta.-hydrogen atoms by N-bromosuccinimide in carbon tetrachloride to .beta.-bromo-.alpha.-keto acid esters; and PA0 by the action of alkali on the dimethanesulphonates and ditoluene-p-sulphonates of .alpha.,.beta.-dihydroxycarboxylic acids.
Methods for preparing arylpyruvic acids also are known. For example, U.S. Pat. No. 4,152,352 discloses the preparation of an arylpyruvic acid by reacting an arylmethyl halide in a liquid solvent medium with carbon monoxide at pressures of 5 to 200 bars in the presence of a catalytic amount of a metal carbonyl compound and an alkaline earth metal inorganic base. Further, U.K. Patent Application No. 2,026,478A discloses that alkali metal salts of an arylpyruvic acid can be prepared by reacting an arylmethyl halide, carbon monoxide and an alkali metal base in the presence of a metal carbonyl compound as catalyst and in the presence of an alcohol or cyclic ether as solvent.